The ultimate goal of this research is to develop a more effective means of identifying individuals at highest risk: for OA progression. These individuals are those in greatest need of an OA prevention strategy. This study will assess the role of and interactions of OA risk factors and surrogate measures. We will prospectively evaluate four measures which individually have been associated with OA progression, late phase bone scintigraphy of the knee, serum levels of cartilage oligomeric matrix protein (COMP), knee alignment, and body: mass index. The study is designed to test the hypothesis that a composite measure which includes al: combination of these four factors, will be more effective at predicting knee OA progression over three years than each of the measures used singly. Progression of OA will be defined as change in narrowest joint space width and change in physical function between baseline and 3 years. The study will also explore the association of COMP level and bone scintigraphy synovial fluid COMP with knee scintigraphy and serum, COMP with total body scintigraphy. Thus, this study will test the secondary hypotheses, that COMP level will be associated with the intensity of radiotracer uptake on late phase bone scintigraphy graded semi-quantitatively. OA that progresses beyond the mild stages is responsible for the bulk of individual and societal costs related to CIA. This study will use a set of validated measures associated with OA progression to improve identification of subjects with established OA most likely to progress and in greatest need of OA, prevention strategies and potentially more aggressive therapeutic interventions. Conversely, the study should elucidate the defining parameters of subjects with lowest risk of OA progression who might otherwise be subjected to potential drug side effects unnecessarily. Finally, the study will use a set of well established OA related factors in a novel way. For example, synovial fluid samples from the index knee joint will be obtained, to test the feasibility and utility of a joint fluid biomarker, COMP, as a prognostic factor for knee OA progression. Also, the capabilities of total body bone scintigraphy will be explored for its utility as a surrogate marker of total body joint burden of active OA joints. The results of these studies could aid in the refinement of subject selection for clinical trials and those most in need of prevention strategies.